Dearomatization Reaction Via η~3-benzyl Palladium Intermediates

Aliphatic carbocycle moieties frequently appear in the molecules of drugs, natural products and functional materials. Dearomatization reaction could afford these alicyclic rings in one step with cheap and readily available aromatic compounds, and the obtained alicyclic rings usually bearing carbon-carbon double bonds provide potential chances for their further functionalization. Therefore, dearomatization reaction as a hot field always attracts the attention of organic chemists. However, the development of dearomatization methods has been a great challenge due to the special stability resulting from the unique structure of aromatic compounds. Over the past four decades, many types of dearomatization reaction, including oxidation, reduction, photocycloaddition, [2,3]-σ-rearrangement, electrophilic addition, nucleophilic addition and other reactions have been developed for breaking up the conjugatedπ-system. In this thesis, the dearomatization reactions throughη3-benzyl palladium intermediates are described.First, the development of a new dearomatization strategy via the nucleophilic substitution ofη3-benzyl palladium intermediates is disscused. The results show that palladium-catalyzed nucleophilic-substitution dearomatization could proceed by an intermolecular or intramolecular reaction. Study on the intermolecular dearomatization demonstrates that phenyl naphthyl methyl chlorides 5d-f and 5h-k are favorable substrates, bothβ-diesters andβ-ketone esters could be used as as nucleophiles. For example, with diethyl malonate as nucleophile, 2-substituted dearomatization products 6d-f and 6h-k were obtained exclusively in 71-93% yields. With methyl diethyl malonate or phenyl diethyl malonate as nucleophile, the reactions exclusively gave 4-substituted dearomatization products 10 and 11 in 92% and 67% yields, respectively.β-ketone esters which show relatively low nucleophilic activity could undergo the dearomatization process under 40℃. For example, with ethyl acetoacetate as nucleophile, 2-substituted dearomatization product 13 was obtained in 42% yield; while using ethyl 2-oxocyclopentanecarboxylate as nucleophile afforded 4-substituted dearomatization product 14 in 71% yield. The intramolecular dearomatization study finds that the reactions of 15a,15b and 15d bearingβ-diester groups at y position of naphthalene ring not only provide dearomatization products but also build new five, six and eight membered alicyclic rings. Among them, the reaction of 15b proceeded efficiently and exclusively provided the 2-substituted dearomatization product 16b in 95% yield.Secondly, the palladium-catalyzed propargylative and allenylative dearomatization of benzylic chlorides and chloromethyl naphthalenes as well as naphthalene allyl chlorides is described. The benzylic chlorides need an activator TBAF to promote the dearomatization reaction, producing the propargylic isomer as the major product. The best result could arrive at 92% yield. However, chloromethyl naphthalenes and naphthalene allyl chlorides could undergo the dearomatization process in the absence of TBAF, which might be due to their relatively high reactivity. With chloromethyl naphthalenes as substrates, allenylative dearomatization products as major product were obtained in 65-96% yields. While the reactions of naphthalene allyl chlorides exclusively gave the propargylative dearomatization products in 62-93% yields.Finally, we studied on the cross coupling reaction of diarylmethyl chlorides with allyltributyltin and ahieved the regioselective control of the coupling reaction with different catalysts. When the reactions were performed in the presence of Pd2(dba)3 and PPh3, allylative dearomatization proceeded to provide satisfactory yields of the desired products. This palladium-catalyzed allylative dearomatization reaction of diarylmethyl chlorides often occurred on the electron-rich benzene ring or the sterically less-hindered naphthalene ring. The rate and yield of dearomatization reaction are depended on the structure of substrates. However, when Cy3P-HBF4 was employed as the catalyst instead of palladium, Stille-type cross-coupling reactions could take place giving more than 89% yield of the corresponding products in 3 hours. The reaction rate and yield do not depend on the structure of substrates.